There is an evidence to suggest that GABA-ergic output to the thalamus from the basal ganglia is directly and/or indirectly involved in pathogenesis of various dyskinesias including parkinsonism and Hungtington's chorea. The present proposal outlines the continued research effort to elucidate the specific role of thalamic areas (ventral medial and ventral anterior nuclei), that receive inhibitory basal ganglia afferents, in the development of dyskinetic disorders. Deafferentation of the thalamus from basal ganglia in adult cats was shown to result in synaptic remodeling in the VA and VM, however, this process takes place at a very slow pace. To clarify the mechanism of this phenomenon data are needed on the interaction of pre- and post-synaptic elements during the lesion induced synaptic remodeling. Since little or no data are available on specifics of synaptic plasticity induced by lesions of inhibitory pathways such studies acquire an additional importance. The specific aims of the present proposal are 1) to determine the nature and the time course of the changes in GABA-receptors in the motor thalamus at short- and long-term survival times after lesions in the reticular part of substantia nigra (SNr) and entopeduncular nucleus (EPN) - a feline homologue of the medial globus pallidus of primates; 2) to determine the changes in Glutamic acid decarboxylase (GAD) containing structures in the neuropil of motor thalamic nuclei under the same experimental conditions. The research will be carried out using the techniques of quantitative receptor binding autoradiography coupled with sophisticated computer image analysis system, and light- and electronmicroscopic GAD-immunocytochemistry. The experimental paradigm is the same used in our current studies on ultrastructural changes in synaptic organization of the thalamus induced by lesions in basal ganglia. Lesions are made by means of stereotactic injections of ibotenic acid in SNr and/or EPN and animals in each of the three experimental groups are studied after short- (1-3 weeks) and long-term (1-7 months) survival times. The neurochemical changes detected in the motor thalamic nuclei will be then interpreted in conjunction with already obtained anatomical data on degeneration and remodeling in the same thalamic nuclei. The results should provide crucially important information on the neurochemical mechanisms and structural correlates of degeneration and plasticity in adult brain related specifically to inhibitory pathways in the motor control system and will be instrumental in further understanding of several aspects of dyskinetic disorders.